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1
Zhou, Hengrui, and 周恆瑞. "Synthesis and characterization of lead compounds in waste lead battery treatment." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/212611.
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Gingras, Marc. "Fluorodemetalation reactions of organogermanium, -tin and lead compounds." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74226.
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Fluoride ions smoothly destannylate organotin oxides, sulfides and selenides to liberate highly nucleophilic species ("S$ sp{2-}$", RS$ sp-$, RO$ sp-$, RSe$ sp-$, etc.). Also, the first nucleophilic oxide "O$ sp{2-}$" and selenide "Se$ sp{2-}$" transfer agents are reported. The tin atom thus serves as a general "group 16 (VIB) transfer agent". In the presence of crown ethers or ammonium salts, this process results in a new way to generate "naked" nucleophiles. Novel anhydrous fluorinating systems (CsF and crown ethers) involving solid-liquid phase transfer catalysis have been designed and studied. In addition, C-C bond forming reactions have been investigated by fluorodestannylation. As an extension of these results, fluorodegermanylation and fluorodeplumbylation reactions are reported. As a generalization, fluoride ion demetalates the whole group 14 for releasing nucleophilic species. Some pentacoordinated intermediates have been observed by $ sp{19}$F and $ sp{119}$Sn NMR spectroscopy in fluorodestannylation, thus confirming the model of nucleophilic substitution at tin and silicon. Mechanistic aspects are discussed along with a possible metal proximity effect in the enhancement of the nucleophilicity of an anion. Finally, in the presence of silver salts, bis(tributyltin) oxide acts as a mild oxygen transfer agent in converting primary organic iodides and bromides to alcohols.
3
Qiao, Boling. "Lead compounds for prion therapeutics from Chinese herbs." Thesis, University of Sheffield, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445123.
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Afolayan, Omolola. "Discovery of antibacterial lead compounds from marine organisms." University of the Western Cape, 2020. http://hdl.handle.net/11394/7914.
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Philosophiae Doctor - PhDMarine organisms including algae and bacteria are known to produce chemically diverse secondary metabolites for survival purposes in the marine environment. Scientists have identified some of these natural products as therapeutic agents including some antibiotics. Given the increase in the resistance of pathogenic microorganisms especially methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis to commonly prescribed antibiotics, researchers have turned towards exploiting marine natural products for new antibacterial compounds. Due to the proven success of finding bioactive compounds in the marine environment this study therefore aims to discover lead compounds against MRSA and Mycobacterium tuberculosis from two marine sources, the marine algae and the bacteria associated with marine invertebrates referred to as bacterial isolates.
2024
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Zhao, Baoshu (Baoshu Eric). "Stabilization of Different Lead Compounds in Portland Cement." Thesis, University of North Texas, 1993. https://digital.library.unt.edu/ark:/67531/metadc278830/.
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Modibane, Kwena Desmond, and Guest. "Synthesis and photophysical properties of antimony and lead phthalocyanines." Thesis, Rhodes University, 2009. http://hdl.handle.net/10962/d1005035.
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This work hereby presents the synthesis, spectroscopic and photophysical properties of newly synthesized lead (PbPc) and antimony (SbPc) phthalocyanines. The complexes are either unsubstituted or substituted at the peripheral and non-peripheral positions with phenoxy, 4-t-butylphenoxy and 4-benzyloxyphenoxy groups. The photophysical properties of these complexes were studied in dimethylsulfoxide, dimethylformamide, toluene, tetrahydrofuran and chloroform as solvents. The fluorescence spectra for PbPc complexes were different to that of the excitation spectra due to demetallation upon excitation. On the other hand, the excitation spectra of oxidized antimony (Sb(V)Pc) derivatives were found to be similar to absorption spectra. High triplet quantum yields for PbPc and SbPc complexes ranging from 0.70 to 0.86, low triplet lifetimes (20–60 μs in DMSO, while they were <10 μs in the rest of the solvents) and low fluorescence quantum yields were observed and is attributed to the presence of heavy atoms (Pb and Sb ions). The nonlinear optical properties of PbPc complexes were studied in dimethylsulfoxide. The optical limiting threshold intensity (Ilim) for the PbPc derivatives were calculated and ranged from 2.1 to 6.8 W/cm2. The photodegradation studies of the PbPc and SbPc complexes synthesized showed that then are stable.
7
Iyer, Ganesh R. "Role of intermetallics for both tin-lead and lead free solder structures and its solder pad combination." Diss., Online access via UMI:, 2005.
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8
Freik, D. M., I. K. Yurchyshyn, L. Yo Mezhylovska, and Ya S. Yavorsky. "Thermoelectricity of Nanostructures Based on Compounds of Lead Telluride." Thesis, Sumy State University, 2012. http://essuir.sumdu.edu.ua/handle/123456789/34878.
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The thermoelectric parameters have been investigated depending on the thickness of the layer of nanostructures
PbTe doped by Bi. Based on the theoretical model of quantum well (QW) with infinitely high walls, it is
demonstrated that this model explains nonmonotonous behaviour of the Seebeck coefficient S and electric conductivity
σ with the change of the well width.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/34878
9
Zhu, Xiaoyu. "Synthesis and Evaluation of Anti-Malarial Compounds Based On an Open Source Lead." Thesis, Griffith University, 2018. http://hdl.handle.net/10072/381517.
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Malaria infection is still considered a major global health problem. According
to the WHO World Malaria Report 2017, 91 countries reported a total of 216 million
cases of malaria in 2016, an increase of 5 million cases over 2015. Furthermore, the
global malaria deaths in 2016 reached 445,000 deaths, which is approximately same
number as was reported in 2015. There is a pressing need for new drugs because
multiple drug resistance now exists, including artemisinin and various partner drugs.
Owing to this situation, this MSc project focused on the potentially lead optimization
of a spirochromanone compound (MMV085230) which constituted part of the
Medicines for Malaria Venture Pathogen Box. This unique source contains 400 diverse
and drug-like molecules that are classified as open source. The Msc project aimed to
synthesise analogues of MMV085230, fully characterise these compounds by
spectroscopy methods, then test all analogues for in vitro antimalarial activity and
analyse data for structure-activity relationships. Using 2-hydroxyacetophenone and its
derivatives to react with 1-Boc-4-piperidone, various spirochromanes were formed.
Following deprotection of the chromanone a number of isocyanates were used to
synthesize a variety of ureas spirochromanone analogues. Furthermore, three
spriochromanone allyl ureas were hydrogenated to give desired compounds. By using
spectroscopy (NMR and MS) and chromatography (flash column and HPLC) techniques, twelve pure compounds were acquired for biological testing.Thesis (Masters)
Master of Science (MSc)
School of Environment and Sc
Science, Environment, Engineering and Technology
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Carbonell, Abigail. "Identification of potential lead antimalarial compounds from marine microbial extracts." Honors in the Major Thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/829.
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Malaria, caused by the parasite Plasmodium falciparum, has a long history as a global health threat. The vector-borne disease causes millions of deaths yearly, especially in developing countries with tropical climates that facilitate transmission. Compounding the problem is the emergence of drug-resistant strains due to overuse of outdated treatments. New compounds with antiplasmodial activity are needed to be developed as effective drugs against malaria. The hypothesis for this project is that marine microorganisms have a high likelihood of yielding novel antiplasmodial chemotypes because of their high diversity, which has not yet been explored for antimalarial development. In this project, microbes harvested and fermented by the Harbor Branch Oceanographic Institute in Fort Pierce, Florida were explored as sources for antiplasmodial natural products. Using a SYBR Green I fluorescence-based assay, 1,000 microbial extracts were screened for inhibition of the multidrug-resistant Plasmodium falciparum strain Dd2. Dose-response analysis was performed on 46 fractions from isolates whose extracts demonstrated greater-than or equal to] 70% inhibition of Dd2 at 1 micro]g/mL. To evaluate cytotoxicity, the MTS cell viability assay was used to calculate IC50 of extracts from active isolates in NIH/3T3 embryonic mouse fibroblasts. Several extracts demonstrated low IC50 in Dd2 and high IC50 in 3T3, suggesting that they contain potential lead antimalarial compounds. Extracts with high selectivity indices (potent plasmodial inhibition with low mammalian toxicity) have been prioritized for dereplication, with the goal of identifying novel active components that can be developed as antimalarial drugs.B.S.
Bachelors
Burnett School of Biomedical Sciences
Molecular Biology and Microbiology
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Braun, Wolfgang. "Study of lead zirconate titanate films grown by MOCVD." Thesis, Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/30420.
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Kirkpatrick, Timothy. "The kinetics of tin solidification in lead-free solder joints." Diss., Online access via UMI:, 2006.
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13
Abell, Russell H. III. "Scavenging of particulate and dissolved lead compounds by coprecipitation with manganese oxyhydroxides." Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/36674.
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Mn is a geochemically important element that contributes significantly to the cycling of heavy metals. During precipitation, Mn oxyhydroxides scavenge many heavy metals, including Pb, in a variety of natural environments. Because of this phenomenon, the precipitation of Mn oxyhydroxides may provide a remediation technique for removing Pb from contaminated aqueous solutions. Therefore, this study was undertaken to provide a quantitative understanding of the coprecipitation of Pb with Mn oxyhydroxides to demonstrate their capacity to remove Pb permanently from contaminated solutions. To accomplish this, a series of factorial experiments with varying initial Mn and Pb concentrations were run in the presence of a borate buffer or a bicarbonate buffer. All experiments were run in batch reactors, in the presence of a quartz substrate, at 25 degrees celcius, at pH 8.5, and were continuously stirred. Initial Mn and Pb concentrations were varied by half log units from 100 to 0 mg/L and from 3 to 0 mg/L, respectively. Solutions were analyzed for Mn using the formaldioxime colorimetric method and for Pb using AA. Precipitates on quartz surfaces were analyzed by SEM, XPS, and XRD for precipitate identification and morphology. The amount of Mn and Pb associated with the quartz sand was determined by dissolving the precipitates from selected quartz samples using concentrated nitric acid. Finally, a different set of precipitate-coated quartz grains were leached in pH 5 acetic acid solution to assess the metal retention capacity of the precipitated material.
Mn oxyhydroxides precipitated onto the quartz sand in both the borate and bicarbonate buffered experiments. SEM and XPS data revealed tiny crystallites in etch pits on the quartz surfaces that contained predominantly Mn3+. XRD analysis did not produce an X-ray pattern for these Mn oxyhydroxides but did identify the suspended Pb precipitates as hydrocerrusite and Pb(HBO3)2 in the borate buffered experiments and hydrocerrusite in the bicarbonate buffered experiments. Much more Mn and Pb are associated with the quartz surfaces in the borate buffered experiments, but no Pb was associated with quartz surfaces initially (< 6 hrs. of reaction time). Leaching of precipitates resulted in extracted Mn in both experiments but Pb was extracted in only the bicarbonate buffered experiments. The Mn precipitation rate was greater in the borate buffered experiments and higher initial Mn and Pb concentrations appear to increase the precipitation rate in both sets of experiments. These results indicate that Mn oxyhydroxides nucleated onto suspended Pb precipitates. The growing Mn oxyhydroxide particles were attracted to the quartz sand, carrying along the Pb precipitates. Further precipitation of Mn oxyhydroxides on the quartz surfaces trapped the Pb. This process was much more significant in the borate buffered experiments where much more Mn precipitated. The greater amount of Mn oxyhydroxide growth acts as a barrier protecting the Pb from the pH 5 leaching solutions. As a result, Pb was retained by the sand grains from the borate buffered experiments during leaching while significant amounts of Pb (35-100%) was extracted from the sand produced by the bicarbonate experiments. These results strongly suggest that coprecipitation of Pb with Mn oxyhydroxides in the presence of a borate buffer and a quartz substrate may be a remediation tool for Pb contaminated aqueous solutions. Not only will this process remove aqueous Pb2+ from solution but it appears it will also substantially incorporate colloidal Pb particles as well.Master of Science
14
Ebiloma, Godwin Unekwuojo. "Identification of new lead compounds for the treatment of African trypanosomiasis." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8340/.
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15
Marucci, C. "NATURAL PRODUCTS AS BUILDING BLOCKS AND LEAD COMPOUNDS FOR API PRODUCTION." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/480029.
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This dissertetion describes the relevance of natural products as building blocks for production of active pharmaceutical ingredients (API) and as lead compounds.
Chapter 1 offers an introduction on the use of natural products as an effective therapeutic and its role on inspiring the discovery of new drugs.
Chapter 2 focuses on the importance of natural products as lead compounds for active pharmaceutical ingredients (API) production. In the first part of this chapter the synthesis of vincamine, the major indole alkaloid presents in Vinca minor L., will be discussed. In particular the design of experiment (DOE) applied to the synthesis of vincamine starting from vincadifformine will be described. In the second part of this chapter the semi-synthesis of two lignan derivatives, oxomatairesinol and (-)-7-(R)-hydroxymatairesinol, will be reported.
Chapter 3 will focus on the isolation and structural characterization of natural products. The first part describes the isolation and structural characterization of ten indole alkaloids from Voacanga africana (Apocynaceae) seeds. Then the semisynthesis of two cytisine derivatives, N-formyl and N-methyl cytisine, will be described.
Chapter 4 describes the role of natural products as lead compounds. The first section illustrate a project that was performed in the laboratory of Prof. Karl-Heinz Altmann (ETH-Zurich, Switzerland) in the frame of COST Action CM1407 (Challenging Organic Synthesis Inspired By Nature: From Natural Product Chemistry To Drug Discovery). It is related to the synthesis of an analogue of the natural product doliculide, a 16-membered depsipeptide, that has been isolated in 1994 from the Japanese sea hare Dolabella auricularia. The second section will focus on the design and synthesis of hybrid compounds. Particularly it will describe the synthesis of pironetin-dumetorine hybrid compounds whose structures are representative of an optimizable lead scaffold for the discovery of new tubulin binders. Another topic here discussed will be the production of bivalent compounds linking two different units, a pironetin-dumetorine hybrid compound and a drug able to bind beta-tubulin, in order to have a duble action with the aim to limit the the protein-protein interaction between alfa and beta tubulin.
Chapter 5 offers an overview on the role of natural products in drug discovery, in particular related to cancer stem cells (CSCs). In a recent review we summarized the natural products that demonstrate activity against CSCs. Forty-nine different natural products grouped into several structural classes (such as flavonoids, polyketides, terpenes, alkaloids and many others) will be described. Their structure diversity could suggest the synthesis of libraries of new compounds for a huge exploration of the chemical space of CSCs inhibitors.
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Caiazza, Daniela. "Crown ethers as potential lead (II) specific probes : a thesis submitted for the degree of Doctor of Philosophy /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phc1328.pdf.
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Johnston, Simon Richard. "Characterisation of basic lead(II) and tin(II) compounds from aqueous systems." Thesis, Brunel University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294510.
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Blais, Jean-Simon. "Determination of alkyllead compounds and synthesis of alkyllead radiotracers." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66177.
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Husein, Maen. "Removal of lead from aqueous solutions with compounds having the sodium carboxylate group." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq29601.pdf.
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Husein, Maen. "Removal of lead from aqueous solutions with compounds having the sodium carboxylate group." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=27228.
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Lead was removed from aqueous solutions using reagents having the sodium carboxylate group. For sodium acrylate and sodium polyacrylate, the removal of lead increased, and the reagent loss decreased when using sodium polyacrylate compared to the monomer, and when using a polymer with higher molecular weight. Sodium propionate did not precipitate lead. Sodium oleate formed a suspension with lead. Sodium caprate formed an easily filterable precipitate. For a feed concentration of 1450 ppm lead, and a mole ratio of caprate to lead of 2, the percentage removal of lead and the percentage loss of caprate were 99.5 $ pm$ 0.2% and 0.8 $ pm$ 0.3%, respectively. The effects of pH, concentrations of lead, calcium, chloride and nitrate in the feed on the removal step were determined. For a certain amount of added caprate, the equilibrium concentrations of lead and caprate were independent of the feed concentration of lead. Decreasing the pH of the feed decreased the removal of lead, but did not affect the loss of caprate. The presence of calcium or nitrate in the feed did not affect the removal of lead. At high chloride concentration, C$ sp circ$(Cl$ sp{-}$) $>$ 0.7 M, the loss of caprate increased slightly. Sodium caprate was recovered by adding HNO$ sb3$ to form capric acid. The sodium caprate was regenerated by adding NaOH. A percentage regeneration of 98.9 $ pm$ 0.3% was achieved.
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Chawner, Stephen John. "Divergent synthesis of cyclopropane-containing fragments and lead-like compounds for drug discovery." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/56635.
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The cyclopropane ring is key to a large number of medicinally‑relevant compounds that possess a broad spectrum of biological activities. This thesis details the preparation of novel bifunctional cyclopropanes through a divergent functionalisation approach utilising two readily accessible cyclopropyl‑scaffolds. The cyclopropanes generated sampled new areas of chemical space whilst being suitable 3‑dimensional fragments and lead-like compounds for drug discovery. A novel CoII-catalysed cyclopropanation generates two diastereoisomeric bifunctional cyclopropyl-scaffolds from commercially available reagents in an excellent yield and can be conducted on multi-gram scales. Asymmetric cyclopropanation has been explored with max ee = 73%. Divergent functionalisation of the ester was explored, utilising hydrolysis, reduction and amidation reactions to create a variety of functionalised cyclopropyl sulfides. The sulfide synthetic handle was oxidised to give the corresponding sulfoxides or sulfone selectively. Sulfoxide–magnesium exchange was explored and the cyclopropyl-organometallic species generated was trapped with a variety of electrophiles to create a diverse range of cyclopropane-containing products. The cyclopropyl-organometallic species was also utilised in Negishi cross-coupling, proving to be a versatile method to attach an aromatic or heteroaromatic directly onto the cyclopropane ring.
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Nokalipa, Iviwe Cwaita. "Synthesis and bioassay of rationally designed DXR inhibitors as potential antimalarial lead compounds." Thesis, Rhodes University, 2017. http://hdl.handle.net/10962/4888.
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Globally, the eradication of malaria has been challenging due to the problem of resistance that past and currently available drugs exhibit. This is exacerbated by the inherent need for anti-malarial drugs to be affordable to the poverty-stricken majority that is primarily affected by this burden. This research has focused on the development of potential inhibitors of 1-deoxy-D- xylulose-5 phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate- independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate into 2-C- methyl-D-erithrytol 4-phosphate. This enzyme has been determined to be a target for the development of novel antimalarial agents and extensive molecular modelling has been undertaken to develop inhibitors that fit into the DXR active site. The in silico docking data have been used to inform the design and synthesis of various N-benzyl-substituted phosphoramidate ligands that were determined to have potential as novel substrate mimics of fosmidomycin, a known DXR inhibitor. Synthesis of the N-benzyl-substituted phosphoramidate ligands involved a nine-step sequence commencing from diethyl phosphoramidate. In all, some 40 compounds have been prepared, some of them new, and were fully characterized using NMR. Attention has also been given to the mass spectrometric fragmentation patterns exhibited by selected intermediates. Four of the final products were evaluated for in vitro antimalarial activity using a PLDH assay and exhibited IC50 values < 100 µM.
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Sekgota, Khethobole Cassius. "Design, development and evaluation of novel lead compounds as HIV-1 enzyme inhibitors." Thesis, Rhodes University, 2015. http://hdl.handle.net/10962/d1017926.
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This project has been concerned with the application of the Baylis-Hillman methodology to the synthesis of medicinally important diketo acid analogues (cinnamate ester-AZT conjugates and 3-hydroxy ester-AZT conjugates) as dual-action HIV-1 IN/RT inhibitors; and on exploratory studies in the preparation of 3-(amidomethyl)-(1H)-2-quinolones as PR inhibitors; and (1H)-2- quinolone-AZT conjugates as dual action IN/RT inhibitors. A series of Baylis-Hillman adducts has been prepared, typically in moderate to excellent yield, by reacting 2-nitrobenzaldehyde with methyl acrylate, ethyl acrylate and methyl vinyl ketone in the presence of 1,4- diazabicyclo[2.2.2]octane (DABCO). Subsequently, various transformations that include conjugate addition of primary and secondary amines to the α,ß-unsaturated moiety to obtain 2- (aminomethyl)-3-hydroxy-3-(2-nitrophenyl)propanoate derivatives, effective SN2´ substitution of the BH ß-hydroxy by a Vilsmeier-Haack in situ-generated chloride to afford Baylis-Hillman allyl chlorides, iron in acetic acid-catalyzed cyclisation to 3-acetoxymethyl-(1H)-2-quinolone derivatives were achieved. Thus, using the Baylis-Hillman methodology, two nuanced classes of diketo acid analogues were constructed. These involved conjugating appropriate propargylamine derivatives with AZT using the „click‟ reaction. In an exploratory study, the quinolone derivative, precisely 3-acetoxymethyl- (1H)-quinol-2-one, was transformed into 3-hydroxymethyl-(1H)-quinol-2-one using potassium carbonate in a mixture of methanol and water (1:1). Following successful hydrolysis, the resulting alcohol was transformed to the corresponding chloride, 3-chloromethyl-(1H)-quinol-2- one, using thionyl chloride. Subsequent nucleophilic substitution afforded 3-(aminomethyl)- (1H)-2-quinolone derivatives which were subsequently transformed to 3-(amidomethyl)-(1H)-2- quinolones; and 3-[(propargylamino)-methyl]-(1H)-quinol-2-one as precursors to quinolone- AZT derivatives. All compounds were characterized by NMR, IR, and where appropriate, high resolution MS
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Vasquez, Valdivieso Montserrat Guadalupe. "Identification of selective inhibitors of phosphofructokinase and fructose bisphosphatase as lead compounds against trypanosomatids." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17980.
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Trypanosomatid parasites cause a wide range of so-called neglected diseases which affect over 27 million people every year. Current treatments are toxic and prone to resistance; therefore, it is imperative to identify novel protein targets and to develop more efficient treatments. Phosphofructokinase (PFK) is the third enzyme in glycolysis, and its reciprocal enzyme in gluconeogenesis is fructose-1,6-bisphosphatase (FBPase); in trypanosomatid parasites (Trypanosoma brucei [Tb], Trypanosoma cruzi [Tc] and Leishmania [Lm] species), both enzymes are recognised drug targets. This thesis describes biochemical and structural studies on these two allosteric enzymes that have been studied with two main purposes: 1) To understand their intrinsic behaviour. The allosteric mechanism of T. brucei PFK is described with the help of two novel crystal structures: TbPFK with the allosteric activator AMP, and mutant A288D located in the effector site. These studies have provided a better understanding of the effect of evolution on the allostery of PFK; and have introduced the first reproducible crystallisation of TbPFK via its A288D mutant. 2) To find novel inhibitors using in silico and high-throughput methods, and to investigate how the intrinsic behaviour relates to the mechanism of inhibition. Nanomolar selective inhibitors against TbPFK and TcPFK have been obtained and optimised to a novel family with low micromolar inhibitory activity against cultured parasites. Crystal structures with three of these inhibitors on TbPFK have helped us understand the structure-activity relationship. Moreover, novel crystal structures of TcPFK and LmFBPase, as well as reproducible crystallisation conditions for the latter enzyme and a mutant of TbPFK (A288D) will undoubtedly facilitate future drug discovery on these targets. Our long-term aim of finding novel drugs against sleeping sickness has been supported by the Wellcome Trust which has recently granted a Seeding Drug Discovery Award with the name “Optimisation of a trypanosome phosphofructokinase lead series to give candidates for treatment of the trypanosomatid based neglected disease Human African Trypanosomiasis”.
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Song, Xun. "To discover antimicrobial lead compounds from three medicinal plants in Lingnan region /Song Xun." HKBU Institutional Repository, 2017. https://repository.hkbu.edu.hk/etd_oa/347.
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Infectious diseases are the major cause of human death worldwide and the need for new generations of anti-infective agents to overcome the drug resistant urgently needs to be tackled. Plant natural products are potential sources of novel antimicrobial compounds. In this study, an investigation into the antimicrobial lead compounds from Michelia figo, Macleaya cordata and Ardisia gigantifolia in Lingnan region is presented. The prevention of dental diseases is targeted at the control of dental biofilm. Streptococcus mutans and S. sobrinus are the leading bacterial strains in the formation of dental biofilm. Extracts of Michellia figo and Macleaya cordata displayed antimicrobial potential in our screening assays. Bioassay-guided isolation of M. figo revealed the presence of artabotryside B and acteoside which were isolated for the first time from this plant. Moreover, chelerythrine and sanguinarine, the two alkaloids isolated from Macleaya cordata displayed the ability to prevent the formation of biofilms of S. mutans and S. sobrinus with the MIC50 values in the range of 18.5-34.0 μM. Anti-TB bioassay-guided isolation of the extract of Ardisia gigantifolia led to isolation of two 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two compounds. Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 μM and 79.2 μM in MABA assay, respectively, and 91.7 μM and 168.3 μM in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 μM in MABA assay and 100.2 μM in LORA assay. Chelerythrine and sanguinarine are the representative and the major active constituents of M. cordata. Both compounds showed significant fungicidal effects in vitro and significant therapeutic effects on guinea pigs of dermatophytosis. Mechanism study for the antifungal efficacy showed that chelerythrine and sanguinarine were potent inhibitors of ergosterol bio-synthesis by reducing the amount of ergosterol without affecting the synthesis of 1,3-β-glucan. In summary, these results highlight the promising antimicrobial activity of chelerythrine, sanguinarine and alkylresorcinols from the medicinal plants in Lingnan region. The active compounds may be regarded as new hits for further study as novel classes of antimicrobial agents for the treatment of infectious diseases.
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Pitt, Melanie A. "Main group supramolecular coordination chemistry : design strategies and dynamic assemblies /." Connect to title online (Scholars' Bank) Connect to title online (ProQuest), 2009. http://hdl.handle.net/1794/10287.
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Saloniemi, Heini. "Electrodeposition of PbS, PbSe and PbTe thin films /." Espoo [Finland] : Technical Research Centre of Finland, 2000. http://www.vtt.fi/inf/pdf/publications/2000/P423.pdf.
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Gupta, Piyush. "Effect of intermetallic compounds on thermomechanical reliability of lead-free solder interconnects for flip-chips." Thesis, Available online, Georgia Institute of Technology, 2004:, 2004. http://etd.gatech.edu/theses/available/etd-08202004-125146/unrestricted/gupta%5Fpiyush%5F200412%5Fmaster.pdf.
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Thesis (M.S.)--Materials Science and Engineering, Georgia Institute of Technology, 2005.Suresh, Committee Member ; C.P. Wong, Committee Member ; Rao R. Tummala, Committee Chair. Includes bibliographical references.
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Bhusaunahalli, Vedamurthy Maheswarappa. "Natural polyphenols as lead compounds in the synthesis of antitumor agents and other useful products." Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/961.
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NATURAL POLYPHENOLS AS LEAD COMPOUNDS IN THE SYNTHESIS OF ANTITUMOR AGENTS AND OTHER USEFUL PRODUCTS
Abstract
Some polyphenol dimers, such as lignans, neolignans and stilbenoid lignans, because of their biological properties as well as their structural variety, are an attractive target for chemical synthesis or modification. These polyphenols may be considered lead compounds to obtain products with useful properties, for instance as possible antitumor agents. Thus, this three year research work has been oriented to the synthesis of new dimers, obtained by biomimetic oxidative coupling of natural polyphenols belonging to the stilbenoid and phenylpropanoid families, namely resveratrol or caffeic acid analogues. To this purpose we employed both chemical and enzymatic methods; in particular, metal-mediated reactions were used for the synthesis of nitrogenated lignans with a benxanthene core, whereas stilbenolignans were also obtained with laccase-mediated reactions. During this work, an unexpected enzymatic reaction afforded an hydantoin-related product and this result is also reported herein.
The results of this research are discussed mainly in chapter 2, where three sections are reported:
1) Biomimetic synthesis of stilbenolignans
2) Biomimetic synthesis of benzo[k,l]xanthene lignanamides
3) Enzymatic synthesis of hydantoin-related compounds
In each section, we have reported in detail the synthesis, structural determination, and mechanism of the formation of the products. The final goal of our project was to obtain a library of bioactive compounds to be addressed to biological evaluation with the aim to establish structure-activity relationships for a future optimization of the most promising products. The biological evaluation has been completed for the stilbenolignan group and it is in progress for the other compounds.
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Pirani, Ayaaz M. "Classically bonded chalcogenide anions of tin, thallium, and lead in basic media /." *McMaster only, 1997.
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Salam, Budiman. "A study of intermetallic compounds formation and growth in Sn-Ag-Cu lead-free solder joints." Thesis, University of Greenwich, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411051.
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Bahar, Mark. "Protoberberine-type Alkaloids as Lead Compounds for the Treatment of African Sleeping Sickness, Leishmaniasis, and Malaria." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1330974078.
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Forsyth, Donald Scott. "Determination of organolead salts in biological tissue." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=73971.
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Guldeste, Ayhan. "Bismuth based thin film superconductors." Thesis, University of Oxford, 1994. http://ora.ox.ac.uk/objects/uuid:681efdc0-8cba-4b3d-83eb-e0021eea5135.
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This thesis describes investigations performed into the growth and characterisation of Bi-based (Bi2Sr2Can-1CunO2n + 4 + x, n=2, 3) ceramic superconducting material in the form of thin films, about 0.5μm thick, grown on single crystal MgO, LaAIO3 and SrTiO3 substrates by r.f. magnetron sputtering. The effect of oxygen content on the Pb doped Bi-2223 (n=3) phase was also studied by changing the cooling process and by annealing in different partial pressures of oxygen at ambient pressure. The films produced have been assessed by considering their initial composition where it is found that Bi/Sr ratios can be between 0.9
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Bhat, Jerome C. "Electroluminescent hybrid organic/inorganic quantum dot devices." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298766.
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Duvenhage, Ingrid. "Structure-activity relationship of methylene blue and its analogues as lead compounds for novel antidepressant development / Ingrid Duvenhage." Thesis, North-West University, 2010. http://hdl.handle.net/10394/4145.
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Antidepressants target serotonergic and/or catecholaminergic responses in an attempt at treating depression yet are at best 65% effective. New antidepressants, as well as new targets for antidepressant action, are thus urgently needed. The nitric oxide (NO)-cGMP cascade is implicated in the pathophysiology of depression. Methylene blue (MB) is a tricyclic compound that is structurally dissimilar to any known antidepressant, inhibits NO synthase (NOS) and guanylate cyclase and demonstrates significant antidepressive-like activity in rodents. The structural-activity relationship of MB and selected analogues will be studied as potential new lead antidepressant compounds using the acute and chronic forced swim test (FST), and compared to imipramine. Those analogues that demonstrate antidepressant-like activity will be studied with respect to their potential to inhibit monoamine oxidase (MAO) -A and –B in vitro, as well as modifying the NO-cGMP pathway in rat hippocampus following sub-chronic treatment.
MB analogues include methylene green (MG), methylene violet (MV), thionin acetate (TA), phenothiazine (PHE), tacrine (TAC) and acriflavine (ACR). MB and MB analogues were tested over a dosage range of 0.5-60 mg/kg in the acute FST study and compared to saline and imipramine. Swimming was analysed with respect to swimming and climbing behaviour to provide an indication of serotonergic and catecholaminergic properties. All the analogues, including imipramine, were tested for their inhibitory action on MAO-A (and B if required) by spectrofluorometric assay using human recombinant MAO. Those analogues with efficacy in the acute FST were tested in the chronic FST following 7 days treatment at the most effective dose identified in the acute FST protocol and compared to imipramine. Hippocampi were removed for analysis of nitrogen oxides, a surrogate marker of NOS activity.
IMI significantly reduced immobility in the acute FST, as did MB and MG, without effects on locomotor activity, thus indicating substantial antidepressant-like activity. ACR, TAC, MV, THI and PHE failed in this regard, while ACR and TAC significantly reduced locomotor activity. MB, MG and imipramine increased climbing behaviour in the acute FST, indicating catecholaminergic potentiation. MB (IC50=0.073 μm), MG (IC50=0.169 μm) and ACR (IC50= 0.43 μm) significantly inhibited MAO-A with moderate inhibition of MAO-B, while IMI and the other analogues were ineffective. In the chronic FST, MG was as effective as imipramine, while MB was more effective than imipramine in reversing immobility, with limited locomotor effects. Interestingly, MB and MG increased swimming behaviour during chronic treatment, indicative of bolstering serotonergic neurotransmission, while imipramine again increased climbing behaviour. Neither imipramine, MG or MB had notable effects on hippocampal NOS. The antidepressant activity of MB and MG involves actions on MAO than on NOS, although MB is a more effective antidepressant than imipramine. Of the various analogues tested, only MG presents with antidepressant-like activity. Both MB and MG are charged entities that have unique structural characteristics, including a dimethylamine substituent at C-3 and C-7, which appears to be a requirement for antidepressant activity. These attributes provide important clues for novel antidepressant drug development.Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2010.
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Mutorwa, Marius Kudumo. "Synthesis of novel inhibitors of 1-Deoxy-D-xylulose-5-phosphate reductoisomerase as potential anti-malarial lead compounds." Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1005037.
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This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
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Stone, Cora Emma. "Neutron studies of amorphous solids." Thesis, University of Reading, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396244.
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PERES, ANA C. "Determinacao de sup210Pb e sup210Po em tabaco de cigarros nacionais." reponame:Repositório Institucional do IPEN, 1999. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10756.
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Made available in DSpace on 2014-10-09T12:43:40Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:09:49Z (GMT). No. of bitstreams: 1 06653.pdf: 2692311 bytes, checksum: 9cf9c14400638383aed081e15b1227b7 (MD5)
Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Huang, Zhiheng. "Materials issues in the transition to lead-free solder alloys and joint miniaturization." Thesis, Loughborough University, 2005. https://dspace.lboro.ac.uk/2134/25232.
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Within the context of the imminent implementation of the Pb-free soldering in Europe in 2006, this thesis addresses the gap in understanding that has emerged in the fundamental materials issues between well-understood and mature lead-containing solders and a plethora of new, Pb-free solders for which there are neither long term reliability data nor understanding of the materials behaviour and how these might be influenced by manufacture and in-service conditions. In addition, this thesis also addresses the question as to whether the solder joint size and geometry could become a reliability issue and therefore affect the implementation of the Pb-free solders in ultrafine micro joints. Thermodynamic calculations using MTDATA (developed by the National Physical Laboratory, NPL, UK) together with a thermodynamic database for solders under either equilibrium or Scheil conditions, have shown their usefulness in Pb-free solder design and processing, generating a wealth of information in respect of the temperature dependence of phase formation and composition. The predictions from MTDATA on a number of selected systems is generally in good agreement with the results from experimental work, and has assisted in the understanding of the microstructure and mechanical properties of the Pb-free solders and the implications of their interactions with a tin-lead solder. However, further critical assessment and the addition of new elements into the solder database, such as Ni and P, are required to make MTDA TA a more effective computational tool to assist the optimization of processing parameters and cost-effective production in using Pb-free solders. Molten solder can interact with the under bump metallizations (UBM) and/or board level metallizations on either side of the solder bump to form intermetallic compounds (IMCs) during solder reflow. In the modelling of the kinetics of the dissolution process of UBM into the liquid solder, the commonly used NernstBrunner (N-B) equation is found to have poor validity for these calculations for micro joints at 100 μm in diameter or less. Three bumping techniques, i.e. solder dipping (SD), solder paste stencil printing followed by reflow (SPR) and electroplating of solders and subsequent reflow (EPR), are used to investigate the interfacial interactions of molten Sn/Sn-rich solders, i.e. pure Sn, Sn-3.5Ag, and Sn-3.8AgO.7Cu, on electroless nickel immersion gold (ENIG) and copper pads at 240°C. The resultant bulk and interfacial microstructures from a variety of pad sizes, ranging from 1 mm down to 25 μm, suggest that in general the small bumps contain smaller β-Sn dendrites and Ag₃Sn IMC particles, nevertheless the interfacial IMC is thicker in the smalI bumps than in the large bumps. In addition, one and two-dimensional combined thermodynamic and kinetic models have been developed to assist the understanding of the kinetics of interdiffusion and the formation of interfacial intermetallic compounds during reflow. Both the experimental results and theoretical predictions suggest that the solder bump size and geometry can influence the as-soldered microstructure, and therefore this factor should be taken into consideration for the design of future reliable ultrafine Ph-free solder joints.
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Oluwafemi, A. J., O. Okanla, P. Camps, D. Muñoz-Torrero, Z. B. Mackey, P. K. Chiang, Scott Seville, and Colin W. Wright. "Evaluation of cryptolepine and huperzine derivatives as lead compounds towards new agents for the treatment of human African Trypanosomiasis." Natural Products Inc, 2009. http://hdl.handle.net/10454/4534.
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noThe alkaloid cryptolepine (1) and eight synthetic analogues (2-8) were assessed for in vitro activities against Trypanosoma brucei. Four of the analogues were found to be highly potent with IC50 values of less than 3 nM and three of these were assessed against T. brucei brucei infection in rats. The most effective compound was 2,7-dibromocryptolepine (7); a single oral dose of 20 mg/Kg suppressed parasitaemia and increased the mean survival time to 13.6 days compared with 8.4 days for untreated controls. In addition, four huperzine derivatives (9-12) were shown to have in vitro antitrypanosomal activities with IC50 values from 303-377 nM.
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Gong, Jicheng. "Microstructural features and mechanical behaviour of lead free solders for microelectronic packaging." Thesis, Loughborough University, 2007. https://dspace.lboro.ac.uk/2134/15102.
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The demands for high density, fine pitch interconnections in electronics systems has seen solder-based approaches for such interconnections miniaturized to the scale of tens of micro meters. At such a small scale, such 'micro joints' may contain only one or a few grains and the resultant mechanical behaviour may not be that for a polycrystalline aggregate, but rather for a single crystal. Since the ~-Sn matrix of SnAgCu solder has a contracted body-centred tetragonal (BCT) structure, such a solder grain is expected to demonstrate a considerably anisotropic behaviour. In such cases the reliability of a Phfree solder is strongly dependent on the local microstructural features, such as the size and orientation of the grains. This thesis presents the investigation of the evolution of microstructure within a joint or at the interface and, the influence of such microstructural features on the meso-scale mechanical behaviour of the Ph-free solder. It includes Evolution of the interface between a molten solder and the Cu substrate To form a joint, the solder alloy is heated and molten, wetting a solid under-bump metallization. After solidification, layers of brittle intermetallic compounds (IMCs) are formed at the interface. In this project, facilities were set up to obtain interfacial reactants at an arbitrary moment of the liquid/solid reaction. Formation and evolution ~ during reflow of SnCu IMCs at the interface between the molten SnAgCu alloy and the Cu UBM was captured and presented for the first time. Formation of phases and IMCs with the body of a liquid SnAgCu solder during solidification The formation behaviour of basic components for a SnAgCu grain (including Sn dendrites, AIDSn and Cu6Sns IMCs) during solidification was investigated. Relationships between the growth behaviour of these components and their internal lattice orientation were studied. The characteristic growth and coupling of AIDSn IMCs and the Sn matrix to form eutectics has been elaborated and presented in this study for - 1- the first time. Based on the results, the forming process of a eutectic SnAgCu grain under the non-equilibrioum solidification condition was illustrated; and major factors that determine the lattice-orientation, size and substructure of the grain were discussed. Meso- and Micro- scale mechanical behaviour of a SnAgCu solder joint To study the size effect on the microstructure, and subsequently, the meso-scale mechanical behaviour, solder joints were manufactured with varying geometries. Shearing tests were performed on these meso-scale joints. The results first demonstrated that the anisotropic characteristics of a SnAgCu grain play an important role in the mechanical behaviour of both a meso-scale solder joint and the adjacent interfacial IMCs. To further investigate the micro-scale deformation and damage mechanisms, micro-mechanical tests were preformed within a SnAgCu grain. Constitutive equations for a SnAgCu grain Based on the experimental results, a crystal model was established to describe the local microstructure-dependent mechanical behaviour. The constitutive equation was implemented by means of the finite element approach, and applied in solder joints of a Flip Chip (FC) package by a multi-scale method. To describe the crystal behaviour at the higher temperature, the model was improved to account for deformations due to vacancy diffusion and thermal expansion. This model was integrated by an implicit approach, and implemented in a full three dimension (3D) finite element (FE) model.
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Lai, Kuei-Hung. "Studies on anti-leukemic terpenoids from medicinal mushrooms and marine sponges with ChemGPS-NP-based targets investigation of lead compounds." Doctoral thesis, Uppsala universitet, Avdelningen för farmakognosi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-317554.
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This thesis investigates the anti-leukemic activity of terpenoids isolated from medicinal mushrooms and marine sponges, as well as their possible targets and mechanisms of action. In the first section, we focused on studying the triterpenoidal components of three triterpenoid-enriched medicinal mushrooms Antrodia cinnamomea, Ganoderma lucidum, and Poria cocos, which have been used in folk medicine for centuries and also developed into several contemporary marketed products. We isolated the major and characteristic triterpenoids from these mushrooms, together with six new lanostanoids (II-1–II-6). The anti-leukemic activity of the isolates was evaluated in vitro using MTT proliferative assay and seven of them exhibited potential anti-leukemic effect. The active lead compounds were further subjected to computational analyses utilizing the ChemGPS-NP tool. We established a database for the anti-leukemic relevant chemical space of triterpenoids isolated from these three medicinal mushrooms, which could be used as a reference database for further research on anti-leukemic triterpenoids. Our results indicated that the anti-leukemic effect of the active lead compounds was mediated not only through topoisomerases inhibition but also through inhibiting DNA polymerases. The second and third sections focused on isolation of anti-leukemic sesterterpenoids from sponges. The investigation of Carteriospongia sp. led to the isolation of two new scalarane-type sesterterpenoids (III-1 and III-2) and one known tetraprenyltoluquinol-related metabolite (III-3). All isolates exhibit an apoptotic mechanism of action against Molt 4 cells, found to be mediated through the disruption of the mitochondrial membrane potential (MMP) and inhibition of topoisomerase IIα expression. Detailed investigation of the apoptotic mechanism of action using molecular docking analysis revealed that compound III-1 might target Hsp90 protein. The apoptotic-inducing effect of III-3 was supported by in vivo experiment by suppressing the volume of xenograft tumor growth (47.58%) compared with the control. In the final section of this thesis we studied manoalide and its derivatives, sesterterpenoids isolated from the sponge Luffariella sp.. Manoalide has been studied as a potential anti-inflammatory agent for the last thirty years with more than 200 publications and 40 patents. However, the configurations at positions 24 and 25 were never revealed. In the current study, ten manoalide-type sesterterpenoids (IV-1–IV-10) were isolated from Luffariella sp. and their stereoisomers at positions 24 and 25 were identified and separated for the first time. The configuration at positions 24 and 25 showed to have a significant effect on the anti-leukemic activity of manoalide derivatives, with the 24R,25S-isomer exhibiting the most potent anti-leukemic activity. The apoptotic mechanism of action of compound IV-7 against Molt 4 cells was investigated, and the compound was found to trigger MMP disruption and intracellular reactive oxygen species (ROS) generation. Compound IV-7 also inhibited activity against both human topoisomerases, I and II. The in vivo experiment further supported the anti-leukemic effect of IV-7 with a 66.11% tumor volume suppression compared to the control.
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Teponnou, Gerard A. Kenfack. "Tacrine, trolox and tryptoline as lead compounds for the design and synthesis of multi-target drugs for Alzheimer's disease therapy." Thesis, University of the Western Cape, 2016. http://hdl.handle.net/11394/5344.
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Magister Pharmaceuticae - MPharmThe cascade of neurotoxic events involved in the pathogenesis of Alzheimer's disease may explain the inefficacy of currently available treatment based on acetylcholinesterase inhibitors (AChEI - donepezil, galantamine, rivastigmine) and N-methyl-D-aspartate (NMDA) antagonists (memantine). These drugs were designed based on the "one-moleculeone- target" paradigm and only address a single target. Conversely, the multi-target drug design strategy increasingly gains recognition. Based on the versatile biological activities of tacrine, trolox and β-carboline derivatives, the attention they have received as lead structures for the design of multifunctional drugs for the treatment of Alzheimer's disease, and the topology of the active site of AChE, we have designed tacrine-trolox and tacrine-tryptoline hybrids with various linker chain lengths. The aim with these hybrids was to provide additive or synergistic therapeutic effects that might help overcome the limitation of current anti Alzheimer's disease drugs. All synthesized compounds were designed from lead structures (tacrine, tryptoline and trolox) to obtain cholinesterase (ChE) multisite binders and multifunctional AD agents. The study was rationalized by docking all structures in the active site of TcAChE using Molecular Operating Environment (MOE) software before proceeding with the synthesis. ChE inhibition was assessed in a UV enzyme inhibition assay using Ellman's method. Antioxidant activities were assessed using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH.) absorbance assay. The hybrids containing the trolox moiety (compounds 8a-e) showed moderate to high AChE inhibitory activity in the nano to micro molar range (IC₅₀: 17.37 - 2200 nM), BuChE inhibition was observed in the same range (IC₅₀: 3.16 – 128.82 nM), and free radical scavenging activities in micro molar range (IC50: 11.48 – 49.23 µM). These are comparable or slightly higher than their reference compounds donepezil (AChE IC₅₀ = 220 nM), tacrine (BuChE IC₅₀: 14.12 nM), and trolox (DPPH IC₅₀: 17.57 µM). The hybrids with longer linker chain lengths, 6 and 8 carbons (8d and 8e), showed better ChE inhibitory activity than the shorter ones, 2, 3, and 4 carbons (8a-c respectively). This correlates well with literature. Free radical scavenging activities, however, seems not to be significantly affected by varying linker chain lengths. The hybrid compound (14) containing the tryptoline moiety linked with a 7 carbon spacer displayed the best AChE and BuChE inhibitory activity (IC₅₀ = 17.37 and 3.16 nM) but poor free radical scavenging activity. Novel anti-Alzheimer's disease drugs with multi-target neuroprotective activities were thus obtained and hybrid molecules that exhibit good ChE inhibition (8d, 8e and 14) and anti-oxidant (8d and 8e) activity were identified as suitable candidates for further investigation.
National Research Foundation (NRF)
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Feltham, Stuart Paul. "An investigation of stoichiometetry and thermo-mechanical processing parameters of (Pb,Bi)â†2Srâ†2Caâ†2Cuâ†3Oâ†x superconducting tapes." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368331.
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Dornerus, Elin. "The effect of rework on brittle fractures in lead free solder joints : The growth of intermetallic compounds during rework and its effects." Thesis, Karlstad University, Karlstad University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-5039.
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Saab Microwave Systems, SMW is a supplier of radar systems. The circuit boards that are operating in their radars have components which solder joints contains lead. However, the EU directive RoHs and WEEE are causing SMW to prepare for a transition to lead free solder joints. The objective of this thesis is to gain deeper knowledge of lead free solder joints.
Brittle fractures in solder joints is a type of failure that might increase in a transition to lead free solder joints. The brittle fractures are induced by the creation of the intermetallic phases which are formed during soldering. The amount and composition of the intermetallics affects the mechanical strength of the joint. An intermetallic layer is thickened during heat exposure as during soldering, thermal aging and rework.
The focus of this thesis was to investigate how rework affect the brittleness of the lead free solder joint and thereby how the intermetallic layers change depending on chemical composition, design and reflow cycles. Two types of components and two types of solder materials (SnPb and SAC305) were studied.
To study the mechanical properties of the joint a shear testing device was used. This is a way of measuring the reliability of the joint when subjected to mechanical shock. The intermetallic layers were examined in a Scanning Electron Microscope and the fracture surfaces were studied in a optical microscope, a scanning electron microscope and a stereomicroscope. The heat spread over the board where examined by soldering thermocouples to the board and plotting the values of time and temperature.
The results showed that the rework process did not have any significant impact of the intermetallic growth. The adjecent and distant components were not damaged during rework. A lead free rework process can therefor be preformed successfully at SMW. The intermetallic layers formed at the interface between the a lead free solder and a nickel finish grew faster than an intermetallic layer formed between a leaded solder and a nickel finish. The presence of nickel could therefore have a more negative effect on the intermetallic growth rate for the lead free material compared to the leaded.
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Thelingwani, Roslyn. "Integration of In Silico and In Vitro ADMET properties in lead identification and optimization of compounds for the treatment of parasitic diseases." Doctoral thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/6889.
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Parasitic infections are the major causes of illness and death in tropical regions especially in Africa. The main parasitic diseases include leishmaniasis, filariasis, malaria, river blindness, Chagas disease and schistosomiasis. With the absence of vaccines, treatment relies mainly on chemotherapy hence the need for efficacious and safe medicines. Many of the medicines currently used have low efficacy and cause side effects. Some are also being lost to drug resistance. To address the inadequacy of treatment options for infectious diseases, a number of initiatives have been started to promote drug discovery and development in Africa. In parallel they have been collaboration between African institutions and leading pharmaceutical companies as well as other relevant R & D organizations. This has led to the need to modernize African approaches to drug discovery and development with respect to the integration of medicinal chemistry, pharmacology and pharmacokinetics as reflected in the processes of Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET). However, scientific and technological expertise in pharmacokinetics for drug discovery is under developed in Africa.
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Waters, Jordan. "A study of the reactivity and coordination chemistry of N-heterocyclic carbenes with main group compounds." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:cda61d5d-da1b-4573-9af9-a1ff28b8d905.
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This thesis describes selected reactivity studies of the N-heterocyclic carbene, IPr, towards a range of main group compounds. The synthesis and characterisation of sixty-three compounds, all of which incorporate IPr as a ligand in one of three coordination modes, are detailed herein. The deprotonation of IPr allowed for the isolation of an anionic source of the aIPr: ligand which was synthesised as a novel potassium salt and along with the previously reported lithium salt, was employed in reactions with group 12 and 14 bis(trimethylsilyl)amides and tetrahalides. The further chemistry of such novel products was investigated towards both electrophilic and nucleophilic reagents making use of both the pendant nucleophilic carbene functionality and the electrophilic main group centre. An alternative route to such species was investigated by the spontaneous isomerisation of IPr in the coordination sphere of group 14 tetrabromides and group 15 tribromides. The scope of this reactivity was subsequently investigated and was found to provide a simpler route to access the abnormal coordination mode of IPr. The aIPr ligand which is generated may be deprotonated by additional IPr thereby affording aIPr: ligands. The addition of halide abstracting agents allowed for the synthesis of cationic species stabilised by the coordination of either IPr or aIPr ligands. A unique, spontaneous reductive coupling of two phosphorus centres was discovered to take place upon heating a THF solution of (IPr)PBr3. This allowed for the isolation of a bromide bridged PâP bond with reduced phosphorus centres. This facile reduction chemistry was further explored by reaction with mild reducing agents which provide access to low oxidation state phosphorus compounds in high yields. This chemistry was found to be possible (and more effective) due to the presence of the weaker phosphorus bond to bromine relative to the commonly employed chlorine ligands.
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Välimäki, M. (Mika). "Discovery of cardioprotective isoxazole-amide compounds targeting the synergy of transcription factors GATA4 and NKX2-5." Doctoral thesis, M. Välimäki, 2018. http://urn.fi/urn:isbn:9789529412525.
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Abstract Acute myocardial infarction is a life-threatening condition that occurs as a result of reduced blood flow in the cardiac muscle, eventually leading to tissue damage. In infarcted areas, cardiomyocytes have insufficient ability to proliferate and replace the injured cells, which is associated with a deficient pumping capacity. A strictly regulated combinatorial interplay of transcription factors, e.g., GATA4, NKX2-5, TBX5, and MEF2C, orchestrates cardiac type gene expression during the cardiomyocyte differentiation and maturation processes. The aim of the present study was to (i) characterize the protein-protein interaction of the cardiac transcription factors GATA4-NKX2-5, (ii) evaluate the chemical agents that modify the synergy of GATA4-NKX2-5 in vitro, (iii) examine the capacity of the lead compound to promote myocardial repair in vivo after myocardial infarction and other cardiac injuries and (iv) study the structural features of the compound important for metabolism and cytotoxicity. Integration of the experimental mutagenic data with computational modeling suggests that the structural architecture of the GATA4-NKX2-5 interaction resembles the protein structure of the conserved DNA binding domain of nuclear receptors. Fragment-based screening, reporter gene-based optimization and pharmacophore searching were utilized to identify the most potent lead compound targeting the GATA4-NKX2-5 interaction: N-[4-(diethylamino)phenyl]-5-methyl-3-phenylisoxazole-4-carboxamide. This compound presented anti-hypertrophic effects in vitro and cardioprotective effects in vivo. In addition, structural analysis of the lead compound revealed the signature molecular features for metabolism and cytotoxicity. Current drug treatments are able to delay, but not prevent the progress of the heart failure; therefore, modulators of protein-protein interactions of key transcription factors may represent a novel class of pharmaceuticals for cardiac remodeling and repairTiivistelmä Sydäninfarkti on henkeä uhkaava verenkierron häiriö, joka syntyy veren virtauksen äkillisen vähentymisen seurauksena sydänlihaksessa aiheuttaen kudosvaurion. Vaurioituneen sydänlihaskudoksen kyky uusiutua tai korvata kuolleet sydänlihassolut uusilla on puutteellinen, ja tämän seurauksena sydämen pumppauskyky heikkenee. Transkriptiotekijöiden GATA4, NKX2-5, TBX5 ja MEF2C muodostamat ja koordinoimat proteiinikompleksit säätelevät sydänsolujen geenien ilmenemistä solujen elinkaaren aikana. Väitöskirjatyön tavoitteena oli (i) karakterisoida geeninsäätelytekijöiden GATA4-NKX2-5 molekyylirakenteet ja niiden keskinäinen vuorovaikutus, (ii) seuloa kemiallisia yhdisteitä, jotka muokkaavat GATA4-NKX2-5 proteiinikompleksin aikaansaamaa geeniaktivaatiota, (iii) tutkia johtoyhdisteen vaikutuksia in vivo sydäninfarktia ja painekuormitusta kuvaavissa eläinmalleissa, ja (iv) tutkia johtoyhdisteen molekyylirakenteen yhteyttä yhdisteen metaboliaan ja sytotoksisuuteen. Väitöskirjatyö osoittaa molekyylimallinuksen ja kokeellisten tulosten perusteella, että geeninsäätelytekijöiden GATA4-NKX2-5 proteiinikompleksin orientaatio matkii tumareseptoriperheen DNA domeenin tertiäärirakennetta. Molekyylifragmenttien, lusiferaasi-reportterikokeen ja farmakoforimallin avulla seulottiin ja optimoitiin sitoutumisvoimakkuudeltaan lupaavin GATA4-NKX2-5 proteiinikompleksin toimintaan vaikuttava johtoyhdiste: N-[4-(dietyyliamino)fenyyli]-5-metyyli-3-fenyyli-isoksatsoli-4-karboksamidi. Johtoyhdisteellä havaittiin solu- ja eläinmalleissa hypertrofiaa estäviä vaikutuksia in vitro ja sydäntä suojaavia vaikutuksia in vivo. Väitöskirjatyö osoitti lisäksi aktiivisten molekyylien rakenneominaisuuksia, jotka keskeisesti vaikuttavat yhdisteiden metaboliaan ja sytotoksisuuteen. Nykyinen lääkehoito hidastaa, mutta ei pysäytä sydänlihasvaurioon liittyvän kroonisen sydämen vajaatoiminnan etenemistä. Lääkevaikutuksen kohdentaminen sydämen keskeisten transkriptiotekijöiden yhteisvaikutukseen avaa uuden mahdollisen tutkimuslinjan sydänlihasvaurion estossa ja korjauksessa
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Yuan, Qiuhua. "Electrochemical Synthesis and Characterization of Inorganic Materials from Aqueous Solutions." Thesis, University of North Texas, 2006. https://digital.library.unt.edu/ark:/67531/metadc5604/.
Full textAbstract:
The dissertation consists of the following three sections: 1. Hydroxyapatite (HA) coatings. In this work, we deposited HA precursor films from weak basic electrolytic solution (pH= 8-9) via an electrochemical approach; the deposits were changed into crystallite coatings of hydroxyapatite by sintering at specific temperatures (600-800 ºC). The formed coatings were mainly characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). XRD patterns show well-defined peaks of HA when sintered under vacuum conditions. FTIR measurements indicate the existence of hydroxyl groups, which were confirmed by the characteristic intensity of the stretching and bending bands at ~3575 and ~630 cm-1, respectively. The SEM shows an adhesive, crack free morphology for the double-layer coating surface of the samples sintered in a vacuum furnace. 2. Silver/polymer/clay nanocomposites. Silver nanoparticles were prepared in layered clay mineral (montmorillonite)/polymer (PVP: poly (vinyl pyrrolidone)) suspension by an electrochemical approach. The silver particles formed in the bulk suspension were stabilized by the PVP and partially exfoliated clay platelets, which acted as protective colloids to prevent coagulation of silver nanoparticles together. The synthesized silver nanoparticles/montmorillonite/PVP composite was characterized and identified by XRD, SEM, and TEM (transmission electron microscopy) measurements. 3. Ce-doped lead zirconate titanate (PZT) thin films. In this study, we fabricated cerium-doped PZT films (molar ratio of Zr/Ti:: 0.5:0.5) via cathodic electrodeposition on the indium tin oxide ( ITO) coated glass substrate. In the preparation process, the PZT films were modified by adding a small amount of cerium dopants, which led to the formation of Ce-doped PZT films after sintering at high temperatures. The fabricated PZT films on the ITO coated glass substrate may be used as electro-optic devices in the industrial application.